ABSTRACT / PROJECT SUMMARY In ?Evaluating Routine Opioid Use during Acute Respiratory Failure?, we propose to study the prescribing practices and long-term ramifications of the routine use of opioids among patients with acute respiratory failure who require mechanical ventilation in the United States. Exposure to prescription opioids may produce opioid- related complications, leading healthcare organizations to increasingly recommend non-opioid alternatives to pain treatment. In contrast to opioid minimization strategies within other healthcare settings, critical care guidelines recommend opioids as the first-line treatment for discomfort that associated with use of a mechanical ventilator. Currently, prescribing patterns for opioids among the approximately 1 million patients in the United States who receive support from a mechanical ventilator for acute respiratory failure are unclear. In addition, changes in opioid prescribing in response to critical care guidelines that recommend opioids as first line pain treatment during mechanical have not been described. Importantly, links between opioids prescribed during mechanical ventilation and long-term opioid use and opioid-related complications remain unexplored. We will use existing longitudinal electronic health record data from complementary sources to efficiently evaluate opioid prescribing patterns and opioid-associated outcomes after critical illness. We have assembled a team with a record of collaboration and expertise in the epidemiology of opioid use, use of electronic health record data to study outcomes after critical illness, and observational research methodology. Our study will benchmark clinical practice for opioid use during acute respiratory failure, and provide insights into the potential risks and benefits of a common, but understudied practice of routine opioid use during mechanical ventilation. Results from our proposal will inform future therapeutic recommendations, and guide the design and conduct of future randomized trials investigating opioid-limited analgesia in the intensive care setting.